 |
||
|
Articles | Departments
| |
||
Tips fromOther Journals
Monitoring Peak Expiratory Flow Rates to Control Asthma
Recommendations for the management of asthma include teaching patients how to monitor their peak expiratory flow rate and adjust their medications accordingly. Patients who are given this information may have a better awareness of their disease and may require urgent treatment for exacerbations of asthma less frequently. Cowie and associates performed a randomized, controlled trial to assess the effectiveness of an action plan based on peak expiratory flow measurements in preventing acute exacerbations of asthma.
The study included 150 adults and adolescents who had required emergency treatment for asthma in the preceding 12 months. All of the patients were given individualized instructions concerning the nature of their disease, asthma triggers, medication use and use of an inhaler.
The patients were randomly assigned to one of three groups. The first group (52 patients) received no action plan. The patients were given verbal information about the variability of asthma and were told that adjustment of their medications might be necessary periodically. The 50 patients in the second group were given written instructions with an action plan based on their symptoms of asthma. The plan included a series of steps whereby they would double the use of inhaled corticosteroids if they noted awakening at night because of asthma symptoms, a persistent cough or symptoms of a cold. They were instructed to begin taking oral corticosteroids if relief from the inhaled bronchodilator lasted less than two hours. They were also told to seek urgent treatment if the bronchodilator provided symptomatic relief for less than 30 minutes or if they were having difficulty speaking. The 48 patients in the third group were given an action plan based on their peak expiratory flow measurements. Each patient was given written instructions about peak flow readings at or below which each step in the action plan should be instituted. A doubling of inhaled corticosteroid dosage was recommended if the peak flow rate was less than 70 percent of the estimated best reading. If the peak flow rate was less than 50 percent, patients were instructed to start taking oral prednisone. If the peak flow rate was less than 30 percent of the predicted value, they were told to seek treatment in the emergency department.
During six months of follow-up, patients who were not given an action plan required 55 visits for urgent treatment of asthma exacerbations. Those following an action plan based on their asthma symptoms required 45 visits for urgent treatment. The difference in the number of urgent care visits was not statistically significant in these two groups. In contrast, only five visits for urgent care were required by the group that followed an action plan based on peak flow measurements. All three groups had a decrease in nocturnal symptoms and in the use of beta2 agonists (an average decrease of 4.45 doses per day by the end of the study). The authors conclude that an action plan based on peak flow measurements is associated with a significant reduction in the need for urgent treatment of asthma.
JEFFREY T. KIRCHNER, D.O.
Cowie RL, et al. The effect of a peak flow-based action plan in the prevention of exacerbations of asthma. Chest 1997 December;112:1534-8.
Aspirin Therapy to Reduce Cutaneous Reactions to Niacin
Niacin has beneficial effects on total cholesterol, high-density and low-density lipoproteins and triglycerides. Unfortunately, niacin is associated with flushing and pruritus that often cause patients to stop taking the drug. Although the use of aspirin can reduce these cutaneous reactions, the most effective dosage has not been determined. Jungnickel and colleagues conducted a randomized double-blind, placebo-controlled trial to compare the effects of pretreatment with aspirin therapy on niacin-induced cutaneous reactions.
Patients between 35 and 65 years of age were included in the study if they had no history of diabetes mellitus, gout, peptic ulcer disease, liver or kidney dysfunction, coagulopathies or hypotension. A total of 22 men and 20 women completed the study. Patients could not ingest caffeine, food or alcohol, and could not smoke within the two hours before taking the study medication. Patients were randomized in a crossover fashion (with seven-day washout periods between treatments) to receive either placebo, 325 mg of aspirin or 650 mg of aspirin for four days, and on the fourth day each patient also received 500 mg of immediate-release niacin 30 minutes after taking the aspirin or placebo. Patients then reported the presence and intensity of flushing, pruritus, tingling, warmth and headache before taking niacin, and at 15, 30, 60 and 120 minutes following niacin administration.
Flushing, itching, tingling and warmth were all significantly decreased by both aspirin regimens, with no differences between the 325-mg and 650-mg doses at any of the times studied. Most patients (60 percent) receiving placebo had a cutaneous reaction of at least moderate severity.
Although cutaneous reactions generally subside once a constant level of nicotinic acid is reached in the blood, the cutaneous symptoms associated with niacin use often prevent this constant level from being reached. The authors conclude that pretreatment with 325 mg of aspirin before administration of niacin can reduce symptoms such as flushing and tingling which may preclude niacin's use. Increasing the dosage to 650 mg does not provide additional benefit.
GRACE BROOKE HUFFMAN, M.D.
Jungnickel PW, et al. Effect of two aspirin pretreatment regimens on niacin-induced cutaneous reactions. J Gen Intern Med 1997 October;12:591-6.
Malaria Prevention in Travelers: Update on Chemoprophylaxis
Nearly 30,000 travelers from Europe and North America contract malaria each year. Keeping abreast of the latest recommendations for malaria chemoprophylaxis can be daunting. Lobel and Kozarsky reviewed the malaria prophylaxis guidelines of the Centers for Disease Control and Prevention and the World Health Organization.
Travelers to sub-Saharan Africa, Papua New Guinea, the Solomon Islands and Vanuatu are at highest risk of contracting malaria, while those traveling to Haiti and the Indian subcontinent are at intermediate risk. The risk is low in most of Southeast Asia and Latin America. Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale and Plasmodium malariae are the four species that cause malaria. Malaria caused by P. falciparum can be fatal if it is not promptly treated.
In addition to chemoprophylaxis, various preventive measures may be taken. These include staying in air-conditioned or well-screened rooms from dusk until dawn, using aerosol insecticides, using mosquito netting and applying N,N-diethyl-m-toluamide (DEET)containing insect repellents on exposed skin. The repellent should contain less than 30 percent DEET, since higher DEET concentrations may be associated with more toxic effects.
Drugs Used in the Prophylaxis of Malaria
The rightsholder did not grant rights to reproduce this item in electronic media. For the missing item, see the original print version of this publication. The spread of resistance to various chemoprophylactic regimens has rendered some drugs much less effective in certain areas of the world. Chloroquine-resistant P. falciparum malaria was first encountered in the 1960s and has spread to most malaria-endemic countries, except Haiti, the Dominican Republic, Central America (west of the Panama Canal) and parts of the Middle East. P. falciparum malaria has also demonstrated resistance to the combination drug pyrimethaminesulfadoxine in Southeast Asia, Africa and the Amazon region, and resistance to mefloquine in western Cambodia and in the regions of the Thai Myanmar and ThaiCambodian borders.
Travelers to areas where chloroquine-resistant malaria occurs should receive mefloquine (see the accompanying table). Mefloquine can be taken by pregnant women and young children. If mefloquine is contraindicated, such as in patients with an underlying neuropsychiatric or seizure disorder, doxycycline prophylaxis is recommended (except in pregnant women and children younger than eight years of age). However, doxycycline is much less effective than mefloquine, and compliance with daily doses of doxycycline may be much lower than compliance with weekly doses of mefloquine.
Chloroquine is still recommended for travelers to areas where chloroquine-resistant malaria has not been reported. This agent can be given to pregnant women and children.
Mefloquine or chloroquine prophylaxis should be initiated one to two weeks before the trip. Doxycycline prophylaxis can be initiated one or two days before the trip. Prophylaxis with mefloquine, chloroquine or doxycycline should continue for four weeks after the patient leaves the area. Primaquine, which is recommended for "terminal prophylaxis" (prophylaxis after travel) to prevent relapsing malaria, should not be taken for more than 14 days.
The authors conclude that none of these treatments is completely effective, so malaria should be included in the differential diagnosis of any ill patient who has returned from a malarious area, even if the patient was compliant with the prophylactic regimen.
GRACE BROOKE HUFFMAN, M.D.
Lobel HO, Kozarsky PE. Update on prevention of malaria for travelers. JAMA 1997 December 3;278:1767-71.
Smoking and Resistance to Insulin in Type 2 Diabetes
Studies have shown that cigarette smoking can impair insulin action in persons with noninsulin-dependent (type 2) diabetes mellitus and in those who do not have diabetes. Other studies have demonstrated that persons who are not diabetic but are chronic cigarette smokers are insulin resistant and hyperinsulinemic when compared with nonsmokers. Cigarette smoking is believed to contribute to hyperglycemia in patients with type 2 diabetes and may possibly accelerate atherosclerosis. Targher and associates examined whether chronic cigarette smoking has an adverse effect on insulin sensitivity in patients with type 2 diabetes.
Forty adult patients of average weight with type 2 diabetes were enrolled in the two-part study. Twenty-eight study subjects were smokers, and 12 were nonsmokers. During the first part of the study, patients were given a 75-g oral glucose tolerance test in which plasma glucose, insulin and C-peptide levels were evaluated at baseline and 30, 60, 90, 120, 180 and 240 minutes after the glucose load for four hours. The second part of the study consisted of a four-hour euglycemic hyperinsulinemic clamp in which glucose was given as a prime-continuous infusion along with a 20 percent glucose solution to achieve a plasma glucose concentration of approximately 90 mg per dL (5 mmol per L). Blood samples were obtained after three hours of using the clamp and then every 10 minutes for the next hour.
Smokers had significantly higher plasma triglyceride and lower high-density lipoprotein (HDL) concentrations. Levels of plasma glucose did not significantly differ between the two groups, whereas levels of plasma insulin and C-peptide were significantly higher among the smokers. While rates of glucose metabolism did not significantly differ between the two groups, the insulin-mediated rate of total glucose disposal was much lower in the smokers.
Metabolic studies suggest that smoking acts by a pathogenetic mechanism to adversely affect insulin sensitivity both in healthy subjects and in smokers. The mildly higher fasting glucose levels in smokers might result in a higher rate of chronic diabetic complications. Patients who smoked also tended to have higher plasma insulin levels, higher plasma triglyceride levels, lower HDL cholesterol and higher systolic blood pressure, all of which are hallmarks of insulin resistance syndrome. Smoking appears to make the insulin resistance of these patients "blossom" with all the attributes of insulin resistance syndrome. As a result, their risk of cardiovascular disease may increase.
The authors conclude that chronic cigarette smoking decreases insulin sensitivity in patients with type 2 diabetes and appears to contribute to insulin resistance syndrome. Further study is needed because the weight gain associated with smoking cessation might also adversely affect insulin sensitivity.
RICHARD SADOVSKY, M.D.
Targher G, et al. Cigarette smoking and insulin resistance in patients with noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab 1997 November;82:3619-23.
Effect of Aerobic Exercise During Chemotherapy
Fatigue and impaired physical performance are common side effects of cancer treatment, affecting up to 70 percent of all patients undergoing radiation treatment or chemotherapy. These problems are due, in part, to inactivity during hospitalization and the acute phase of treatment. Dimeo and colleagues evaluated the effects of aerobic exercise on the loss of physical performance in patients undergoing high-dose chemotherapy followed by autologous peripheral blood stem cell transplant. The impact of aerobic activity on the incidence and severity of complications during this treatment was also reviewed.
Eighty patients between the ages of 18 and 60 years with solid cancerous tumors were considered for enrollment in the study. Of that group, 70 were randomly assigned to one of two groups. Thirty-three patients were assigned to a regular exercise protocol during treatment, while the remaining 37 were assigned to the control group with no intervention. One week before starting chemotherapy, all patients underwent a treadmill stress test to determine baseline physical performance.
Patients in the training group followed a daily regimen in which they "biked" on a bed ergometer for one minute in order to reach at least 50 percent of their cardiac reserve, then rested for one minute. This exercise-rest regimen was performed 15 times, so patients were training for 30 minutes a day. In addition, complete blood cell counts and serum chemistry measurements were obtained each day 12 hours after training. On the day of discharge, patients in both groups underwent resting electrocardiography, echocardiography and a treadmill stress test. Hematologic and nonhematologic toxicities also were assessed at this time.
At the beginning of the study, the baseline physical performance of both groups was the same. After hospitalization with no exercise, patients in the control group had a 27 percent higher loss of physical function than those in the exercise group. Hemoglobin and hematocrit levels were similar for both groups at the beginning and end of the study, but the training group had a shorter duration of neutropenia and thrombocytopenia. In addition, patients in the treatment group reported less severe pain and diarrhea, less need for analgesics and a shorter average hospital stay than those in the control group. During the exercise program no injuries to the patients were reported.
The authors conclude that initiation of an aerobic exercise program immediately after high-dose chemotherapy is safe and may prevent severe loss of physical performance. Exercise may also decrease some of the toxic side effects associated with chemotherapy.
KARL E. MILLER, M.D.
Dimeo F, et al. Effects of aerobic exercise on the physical performance and incidence of treatment-related complications after high-dose chemotherapy. Blood 1997 November 1;90:3390-4.
Coronary Angioplasty vs. Thrombolytic Therapy
Percutaneous transluminal coronary angioplasty (PTCA) is more widely used for revascularization following acute myocardial infarction than intravenous thrombolytic therapy, and PTCA seems to have the advantage of higher initial reperfusion rates. Weaver and associates combined data from trials of PTCA and thrombolytic therapy to determine each treatment's effect on death, reinfarction, major bleeding, total stroke and hemorrhagic stroke.
A literature search of MEDLINE and queries to principal investigators identified 10 randomized trials that compared PTCA and thrombolytic therapy. The only criterion for inclusion in the analysis was the use of PTCA or any course of intravenous thrombolytic therapy. These studies yielded data on 2,606 patients.
A total of 1,290 patients underwent PTCA. Of the 1,316 who received thrombolytic therapy, 307 received streptokinase, 300 received a three- or four-hour infusion of tissue-type plasminogen activator (t-PA), and 709 received a rapid infusion of t-PA.
The risk of death was significantly lower in patients undergoing PTCA (odds ratio: 0.66). The mortality rate at 30 days or less was 4.4 percent in the PTCA group, compared with 6.5 percent in the thrombolytic therapy group. The rate of nonfatal reinfarction was 5.4 percent for PTCA and 2.8 percent for thrombolytic therapy. The pooled rates of death or nonfatal reinfarction were 7.2 percent for PTCA and 11.9 percent for thrombolytic therapy. The total rate of stroke also was lower in the PTCA group, as was the rate of hemorrhagic stroke. The rate of hemorrhagic stroke was highest in patients receiving t-PA, although major bleeding rates were similar for PTCA and thrombolysis (8.8 percent and 8.4 percent, respectively).
The authors conclude that PTCA appears to be superior to thrombolytic therapy for treatment of acute myocardial infarction. They note that their retrospective meta-analysis has limitations because of differences, including the way PTCA was performed, in the treatments utilized in the trials they evaluated. The authors state that long-term assessment of outcomes is needed, and individual hospitals must examine their own results to determine if PTCA should be favored over thrombolytic therapy in their institution.
GRACE BROOKE HUFFMAN, M.D.
Weaver WD, et al. Comparison of primary coronary angioplasty and intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review. JAMA 1997 December 17;278:2093-8.
Patient Preferences for Colorectal Cancer Screening
Patient preferences with respect to colorectal cancer screening have not been well studied. Dominitz and Provenzale evaluated patient preferences about colorectal screening using time trade-off issues as a measurement.
Four groups of patients were interviewed using a structured format that included time trade-off issues. Time trade-off has previously been shown to be a reliable tool for estimating the quality of life related to a variety of health states. The four groups consisted of 46 patients with colorectal cancer, 24 patients who were scheduled to undergo screening flexible sigmoidoscopy, 114 patients scheduled to undergo screening colonoscopy and 62 patients who had never undergone a colorectal cancer screening procedure. The interview covered quality-of-life issues concerning colorectal screening, current health status, colorectal cancer and colostomy.
The patients who had never undergone colorectal cancer screening were willing to trade off a median of 91 days of life expectancy to avoid a screening flexible sigmoidoscopy and a median of 183 days to avoid a colonoscopy. Patients in the other three groups were not willing to trade off any amount of life expectancy. Although 50 percent of the patients who had never undergone screening would have traded less than three months of life expectancy to avoid sigmoidoscopy every five years, 25 percent stated they would surrender a year or more of life expectancy to avoid sigmoidoscopy. Some of the patients had strong preferences for sedation during an endoscopic procedure, suggesting that colonoscopy may be appropriate in such patients. Other patients did not feel at ease with limiting the screening procedure to sigmoidoscopy.
The authors conclude that the majority of patients find endoscopy to be an acceptable procedure for colorectal cancer screening. However, some patients were willing to surrender more life expectancy to avoid these procedures. To address these issues, physicians must develop alternative strategies for patients whose preferences do not match the standard recommendations for colorectal cancer screening.
KARL E. MILLER, M.D.
Dominitz JA, Provenzale D. Patient preferences and quality of life associated with colorectal cancer screening. Am J Gastroenterol 1997 December;92:2171-8.
Mibefradil: A T-Type Calcium Channel Blocker
Mibefradil dihydrochloride, a nondihydropyridine calcium channel blocker, has been approved by the U.S. Food and Drug Administration for the treatment of hypertension and chronic stable angina. This agent is the first T-type (transient) calcium channel blocker. Consultants for The Medical Letter on Drugs and Therapeutics reviewed the available data on this new drug.
All of the currently available calcium channel blockers prevent calcium influx in L-type (long-acting) channels throughout the vascular system and myocardium. Mibefradil also blocks T-type calcium channels, which are activated at lower voltages and are found in vascular smooth muscle and the myocardial conduction system but not in the ventricular myocardium. Mibefradil produces coronary and peripheral vasodilation without reflex tachycardia. It is not known whether mibefradil's T-type calcium channel activity offers any advantage over older calcium channel blockers.
Studies comparing the antihypertensive effects of mibefradil with those of other calcium channel blockers indicated that mibefradil was more effective in blood pressure reduction than diltiazem and about as effective as amlodipine and nifedipine. In one study, the addition of an angiotensin converting enzyme inhibitor to mibefradil therapy was found to increase the antihypertensive effect.
Two controlled studies of the use of mibefradil in chronic stable angina demonstrated that this agent was more effective than placebo in delaying the onset of ischemia during exercise and in increasing exercise tolerance. A large trial of the use of mebefradil in patients with congestive heart failure is currently under way.
Like other calcium channel blockers, mibefradil causes a slight decrease in heart rate. Sinus bradycardia, first-degree atrioventricular block and asymptomatic Wenckebach-type block can occur with use of mibefradil. Third-degree block has not been reported when the drug is taken at recommended dosages; however, higher dosages have been associated with QT changes.
Patients with sick sinus syndrome or second- or third-degree atrioventricular block without a pacemaker should not take mibefradil. This drug should not be used in patients taking terfenadine, astemizole or cisapride because of the risk of fatal arrhythmias if plasma concentrations increase. Syncope has been noted with mibefradil, particularly in elderly patients who are also receiving a beta blocker. Plasma levels of tricyclic antidepressants and cyclosporine can increase with concomitant administration of mibefradil, and dosage adjustment may be necessary.
Side effects reported with mibefradil include dizziness, fatigue and lightheadedness. In studies comparing mibefradil with other calcium channel blockers, peripheral edema has occurred less frequently with use of mibefradil than with diltiazem, nifedipine and amlodipine.
The recommended starting dosage of mibefradil in the treatment of patients with either hypertension or chronic stable angina is 50 mg daily, which can be increased to 100 mg once daily. Mibefradil should be used cautiously in patients with liver dysfunction.
BARBARA APGAR, M.D., M.S.
Medical Letter consultants. Mibefradil--a new calcium-channel blocker. Med Lett Drugs Ther 1997 November; 39:103-5.
Long-term Amphetamine Use in Children with ADHD
Approximately 2 percent of school-aged children in the United States are currently being treated with stimulant medications for attention-deficit hyperactivity disorder (ADHD). These medications have been found to be extremely effective, with response rates of 70 to 96 percent. Mild side effects, including weight loss and insomnia, are frequent and are considered to be dose dependent. To date, studies of the effect of stimulants on children with ADHD have been mainly short term. Two long-term studies did not show clear benefits of stimulant medication in the treatment of ADHD. Gillberg and associates performed a randomized, double-blind study to evaluate the long-term effects of amphetamine use in children with ADHD.
Children enrolled in the study were between six and 11 years of age. Each child was evaluated by a child psychiatrist and a psychologist, and had to meet at least eight of the 14 symptom criteria for ADHD in the Diagnostic and Statistical Manual of Mental Disorders (3d ed rev). Exclusion criteria included an IQ of less than 50 or a chronic medical condition such as diabetes, cardiovascular disease or neurologic disease. At baseline, all children received amphetamine, which was titrated to an effective level over a three-month period. The children were then randomized to receive either amphetamine or placebo for 12 months. This regimen was followed by a three-month period of single-blind placebo treatment. Clinical examination and questionnaires, including the Conners Teacher Rating Scale, Conners Parent Rating Scale and the Wechsler Intelligence Scale for ChildrenRevised (WISCR), were performed at baseline and at three-month intervals until the end of the 18-month study period.
A total of 62 children (51 boys, 11 girls) were included in the study. There were no major differences between the two treatment groups. All children responded to stimulants during the first three months of the study with an average decline in Conners rating scores of 27 to 47 percent. During the 12-month double-blind phase, children treated with amphetamine had a significantly greater increase in WISCR scores at nine months or more compared with the placebo group. Results of the Conners rating scales, which originally declined with treatment in all children, increased up to six months after placebo was given. The Conners rating scores remained lower in the treatment group throughout the duration of the study. Side effects were more common in the amphetamine group but did not differ significantly in terms of incidence. The one exception was a decrease in appetite that occurred in 17 of the children in the treatment group and in two children who received placebo.
During the 12-month double-blind phase of the study, 71 percent of the placebo group and 29 percent of the amphetamine group stopped treatment or went on to open treatment. However, this high rate of withdrawal was anticipated and strongly suggests the superiority of the stimulant drug versus placebo for treating ADHD. Approximately 14 percent of the original cohort of patients were classified as non-responders or dropped out as a result of severe side effects.
The authors conclude that stimulant medications remain effective in the treatment of ADHD for at least 15 months after initiation of therapy. Positive effects include a decrease in hyperactivity and behavior problems, as well as a tendency for improved learning. In addition, side effects do not seem to increase with a longer duration of treatment.
JEFFREY T. KIRCHNER, D.O.
Gillberg C, et al. Long-term stimulant treatment of children with attention-deficit hyperactivity disorder symptoms. A randomized, double-blind, placebo-controlled trial. Arch Gen Psychiatry 1997 September;54:857-64.
Mammography Before Age 50 and Rate of Cancer Mortality
Previous studies have suggested that women under the age of 50 should receive mammographic screening more frequently than every two to three years to reduce their mortality rate from breast cancer. Bjurstam and associates evaluated the impact of mammography every 18 months on breast cancer mortality among women aged 39 to 49 years as part of the Gothenburg Breast Screening Trial.
Between September 1983 and April 1984, a total of 11,724 women aged 39 to 49 years were invited to begin receiving mammographic screening every 18 months. Two-view mammograms were performed unless earlier examinations indicated that a single view was adequate for screening. These women were matched with 14,217 women who did not undergo mammographic screening until the sixth or seventh year of the study.
During the study period, breast cancer was diagnosed in 144 women in the mammographic screening group and in 195 women in the control group. Eighteen women in the screening group died of breast cancer compared with 40 women in the control group, representing a 45 percent reduction in mortality from breast cancer. In women who were compliant with the recommended 18-month interval, the reduction in mortality increased to 49 percent.
The authors conclude that an 18-month screening interval for mammography in women aged 39 to 49 years has a significant impact on reducing breast cancer mortality. Organizations that develop mammographic screening recommendations should consider these new findings when formulating mammography guidelines for women under 50 years of age.
KARL E. MILLER, M.D.
Bjurstam N, et al. The Gothenburg Breast Screening Trial: first results on mortality, incidence, and mode of detection for women ages 39-49 years at randomization. Cancer 1997 December;80:2091-9.
Efficacy and Safety of Topical Gel for Actinic Keratoses
Actinic keratoses are sun-induced premalignant lesions that occur more commonly in older or immunosuppressed persons, males and people with fair skin. Untreated lesions can develop into squamous cell carcinoma. Current treatments such as cryotherapy, curettage or topical treatment with fluorouracil have the potential to cause considerable discomfort and are poorly tolerated. A number of nonsteroidal anti-inflammatory drugs (NSAIDs) have been found to affect the growth profile of some tumors and may offer potential benefit for the treatment of actinic keratoses. As the geriatric population in the United States increases, the prevalence of these lesions will probably continue to increase. Rivers and McLean performed an open-label study of topical 3 percent diclofenac in 2.5 percent hyaluronic acid gel to determine its effectiveness in the treatment of actinic keratoses.
Study participants were instructed to apply 1 g of the gel to one or more actinic keratoses twice daily for as many as 180 days. A total of 29 adults were treated for periods of 33 to 176 days and were assessed by both visual and photographic methods. Twenty-seven patients were reevaluated 30 days after they discontinued using the gel. Of the 27 patients, 22 (81 percent) had a complete response, and another four (15 percent) showed marked clinical improvement. Thirty days later, results were more dramatic, with a nearly complete response in all subjects. In the 22 patients whose lesion response was considered complete, the mean time to complete resolution was 94 days.
When study participants assessed the efficacy of the gel after treatment was discontinued, 45 percent thought the results were excellent, 10 percent rated the results as good, 10 percent rated the results as fair and 34 percent thought the results were poor. After the study was completed, the tubes of gel were weighed to assess compliance. Approximately 50 percent less gel was used than expected. Ten study participants were found to have used more than the 1 g per day recommended, and 14 participants had used less than 1 g daily.
The only clinically relevant adverse effects were those related to skin irritation, which occurred in 21 patients (72 percent). In the seven patients who experienced irritant contact dermatitis at the treatment site, the drug was discontinued and the reaction resolved within one to two weeks. On provocative testing, the eczematous reaction appeared to be irritant rather than allergic in nature.
Topical 3 percent diclofenac in 2.5 percent hyaluronic acid gel was highly effective in reducing or completely eliminating the actinic lesions. Lesions continued to improve even after treatment ceased. Thirty days after treatment, the lesions were considered clinically clear in 81 percent of the patients.
The authors conclude that 3 percent diclofenac in 2.5 percent hyaluronic acid gel has promise as a first-line topical therapy in the treatment of patients with actinic keratoses and should be compared with other commonly used NSAIDs in prospective trials.
BARBARA APGAR, M.D., M.S.
Rivers JK, McLean DI. An open study to assess the efficacy and safety of topical 3% diclofenac in a 2.5% hyaluronic acid gel for the treatment of actinic keratoses. Arch Dermatol 1997 October;133:1239-42.
Physical Function, Mobility and Development of Kyphosis
The lifetime risk of vertebral fracture is estimated to be nearly twice as high as the risk of hip fracture in women older than 50 years. A common sequela of vertebral fracture is the development of kyphosis, causing deformed posture and potentially impaired pulmonary function. Ryan and Fried assessed the impact of kyphosis on physical function and mobility.
The study included 231 women aged 59 to 89 years who were living in the community. Women were excluded from participation if they could not stand unaided for 30 seconds or if their Folstein Mini-Mental Status Examination score was less than 18. Kyphosis was classified as mild (slight rounding of the upper back and shoulders), moderate (a definite "widow's hump") or severe (inability to raise the head level). Mobility was assessed by means of various performance-based tests, such as the time required to walk 5 meters (5.5 yards) and the time required to walk up and down a flight of stairs.
A majority of the women (57 percent) reported a diagnosis of arthritis, but only 11 percent reported a diagnosis of osteoporosis. Fewer than 1 percent reported a history of vertebral fracture. Twenty-seven percent of the women had no kyphosis. Kyphosis was mild in 42 percent, moderate in 26 percent and severe in 5 percent of the women. Quantitative measures of the kyphosis ranged from zero to 15 cm. An increased degree of kyphosis was associated with longer walking and stair-climbing times. Kyphosis also affected the ability to reach for objects and perform heavy housework.
The authors conclude that osteoporosis, with consequent kyphosis, may have even more of an impact on a patient's functional level than was previously thought. Only 11 percent of the women in this study knew that they had osteoporosis, yet 31 percent had moderate or severe kyphosis. The impact of kyphosis may be a consideration in counseling patients on the prevention and treatment of osteoporosis.
GRACE BROOKE HUFFMAN, M.D.
Ryan SD, Fried LP. The impact of kyphosis on daily functioning. J Am Geriatr Soc 1997 December;45:1479-86.
Quality of Hospital Care and Pneumonia in the Elderly
The most frequent infectious cause of death in the United States is pneumonia. The Health Care Financing Administration (HCFA) is interested in assessing the quality of care in Medicare patients admitted to the hospital because of pneumonia and in determining what performance measures are associated with improved survival. Meehan and colleagues reviewed the medical records of 14,069 elderly patients hospitalized with pneumonia to evaluate these issues.
A standardized data collection system was used to collect information about four quality of care indicators in patients hospitalized because of pneumonia: (1) the interval between hospital arrival and administration of antibiotics, (2) whether blood cultures were collected before antibiotic therapy was instituted, (3) whether blood cultures were obtained within 24 hours of hospital arrival and (4) whether oxygenation status was assessed within 24 hours of hospital arrival.
Cases of pneumonia were identifed by HCFA from the Medicare National Claims History File. Patients were excluded from the study if they were under 65 years of age, had human immunodeficiency virus (HIV) infection, had recently been exposed to chemotherapy or immunosuppressive therapy or had been transferred from another acute care facility. Severity of illness variables, process of care variables (such as the rapidity of initial administration of antibiotic therapy, the time of blood culture collection and oxygenation assessment) and outcomes of care were evaluated.
Approximately 25 percent of the patients were transferred to the hospital from skilled or intermediate nursing care facilities. Most of the study subjects (58.2 percent) had at least one other illness. Antibiotic therapy was initiated within eight hours of admission in 75.5 percent of the patients.
The risk of death at 30 days increased as the interval between hospital admission and initiation of antibiotic therapy increased beyond eight hours. Similarly, the risk of death at 30 days was significantly lower in those patients in whom blood cultures were obtained within 24 hours of admission. Whether blood cultures were collected before or after antibiotic administration had no significant effect on 30-day mortality.
The authors conclude that the findings of this retrospective review encourage speedy antibiotic administration and blood culture collection in elderly patients with pneumonia. Wide variation was found in the interval between hospital admission and implementation of these two measures, suggesting an area for improvement in the hospital care of elderly patients with pneumonia.
GRACE BROOKE HUFFMAN, M.D.
Meehan TP, et al. Quality of care, process, and outcomes in elderly patients with pneumonia. JAMA 1997 December 17;278:2080-4.
Identifying and Treating Acute Ischemic Stroke
Effective treatment of acute ischemic stroke requires rapid assessment and early intervention. Currently, the only effective therapy is thrombolysis with tissue plasminogen activator (tPA) within three hours after the onset of stroke. However, a number of potential delays make early diagnosis and treatment difficult. Kasner and Grotta review the pathophysiology of cerebral ischemia and the implications for treatment, identify some of the potential delays that commonly occur in diagnosing stroke and offer ways to expedite diagnosis and treatment.
Stroke occurs as a result of a specific sequence of events that happen after abrupt interruption of blood flow to the brain. The level of brain injury depends on the severity and duration of ischemia. In the hours after stroke, cytokines and cell adhesion molecules stimulate local inflammation, which further impairs blood flow. Reperfusion must occur within three hours of the onset of symptoms to preserve a substantial portion of the brain tissue at risk.
Treatment of acute stroke focuses on restoring cerebral perfusion and protecting neural tissue. Thrombolysis with tPA has demonstrated a positive effect on reperfusion since tPA converts plasminogen to plasmin, which causes cleavage of fibrin and ultimately results in rapid lysis of the clot. At this time, neuroprotective therapies and streptokinase are not effective in the treatment of acute stroke. For tPA to be effective, however, early diagnosis and rapid intervention are essential; patients targeted for tPA intervention must meet very specific inclusion and exclusion criteria to reduce the risk of hemorrhage (see accompanying table). In addition, careful analysis of the initial computed tomographic (CT) scan also appears to be critical in reducing the risk of intracranial hemorrhage. During the first 24 hours, patients given tPA cannot take anticoagulant and antiplatelet agents.
Inclusion and Exclusion Criteria for Thrombolysis of Acute Ischemic Stroke with tPA
- Inclusion criteria
- Age >18 years
- Clinical diagnosis of ischemic stroke, with onset of symptoms within three hours of initiation of treatment
- CT (noncontrast) without evidence of hemorrhage
- Exclusion criteria
- Historic
- Stroke or head trauma in previous three months
History of intracranial hemorrhage that may increase risk of recurrent hemorrhage
Major surgery or other serious trauma in previous 14 days
Gastrointestinal or genitourinary bleeding in previous 21 days
Arterial puncture at a noncompressible site in previous seven days
Lumbar puncture in previous seven days
Pregnant or lactating woman- Clinical
- Rapidly improving stroke symptoms
Seizure at onset of stroke
Symptoms suggestive of subarachnoid hemorrhage, even if CT is normal- Persistent systolic blood pressure >185 or diastolic blood pressure >110 mm Hg,
or requiring aggressive therapy to control blood pressure- Clinical presentation consistent with acute myocardial infarction or post-
myocardial infarction pericarditis requires cardiologic evaluation before treatment- Radiographic
- CT with evidence of hemorrhage
CT with evidence of hypodensity and/or effacement of cerebral sulci in more than one third of middle cerebral artery territory- Laboratory
- Glucose <50 or >400 mg per dL (<2.7 or >22.2 mmol per L)
Platelets <100,000 per mm3 (100,000 3 109 per L)
Warfarin therapy with a prothrombin time >15 seconds
Heparin therapy within 48 hours, and elevated partial thromboplastin time
tPA=tissue plasminogen activator; CT=computed tomography.
Reprinted with permission from Kasner SE, Grotta JC. Emergency identification and treatment of acute ischemic stroke. Ann Emerg Med 1997;30:644.
Delays in recognition and treatment can be summarized by using the four D's: door (time until treatment), data (obtaining an electrocardiogram), decision (choice of therapy with thrombolysis) and drug (choice of agent). Education among health care providers at all levels and among the public as well is needed to expedite stroke treatment. Within the hospital, the use of a "stroke team" composed of neurologists, emergency physicians and nurses, along with radiologists and pharmacists, is appropriate to streamline diagnostic testing and emergency care of patients with signs and symptoms of stroke. If the criteria for thrombolysis are met, tPA infusion should be initiated in the emergency department, and the patient should be monitored closely for 24 hours.
The authors conclude that time is the most critical element in the successful treatment of an acute ischemic stroke. Since neural tissue is extremely sensitive to ischemic injury, thrombolysis with tPA should occur within three hours of the onset of symptoms if the patient meets the criteria for this therapy. Care of acute stroke must parallel that of acute myocardial infarction in ensuring early diagnosis and rapid intervention. A door-to-drug interval of 60 minutes is recommended as part of successful management.
RICHARD SADOVSKY, M.D.
Kasner SE, Grotta JC. Emergency identification and treatment of acute ischemic stroke. Ann Emerg Med 1997 November;30:642-53.
Diagnosis of Insufficiency Fracture in the Elderly
Physicians are seeing an increasing number of patients with stress fractures as a result of the emphasis on physical fitness in the general population. Elderly persons also are exercising more than in the past, either to keep fit or as part of a therapeutic regimen for a particular health problem and, as a result, they too sustain stress fractures. In elderly patients, however, stress fractures may be a result of lack of regular physical activity or the inability of the musculoskeletal system to withstand the stress of exercise. Stress fractures in some elderly patients actually may be insufficiency (fatigue) fractures because they affect bone with lower resistance. Carpintero and colleagues evaluated the incidence of insufficiency fractures in the elderly population and associated factors, such as exercise type, symptoms, diagnostic delays and treatment.
The medical records of 6,650 patients who visited an orthopedic care unit over a six-year period were reviewed to identify the incidence of stress fracture in the elderly. Patients were included in the study if they were older than 60 years of age and had a definitive diagnosis of insufficiency fracture as established by findings on radiography or scintigraphy. Other factors evaluated included gender, type of exercise, examination findings, bone and side affected, delay in diagnosis, bone mass, treatment and treatment outcomes.
All of the 30 stress fractures that occurred in the study subjects were in the lower limbs, primarily the tibia. Thirteen of the patients (43 percent) were men, 17 (57 percent) were women. Brisk walking was the cause of injury in 17 patients (56.6 percent), running was the cause in 10 patients (33.3 percent) and hunting was the cause in three patients (10.0 percent). In most cases, studies of bone mass were within normal limits for the patient's age but were lower than that of a young person. In all cases but one, pain was the symptom that prompted the physician visit but usually only after pain relief was attempted at home. As a result, diagnosis was delayed between one and nine months in most patients, with an average delay of 4.9 months. The average delay in initiating physician contact after the onset of symptoms was three months.
The authors conclude that elderly patients involved in any type of physical activity on a regular basis may sustain insufficiency fractures. Decreased bone mass was implicated in the greater percentage of these fractures in women. Stress fractures may occur in both extremities and in the spine in younger patients. However, in the study population, all cases of stress fracture occurred in the lower extremities. Therefore, lower extremity pain in an elderly patient should be evaluated and, if the patient exercises regularly, a diagnosis of insufficiency fatigue fracture should be considered. Prompt diagnosis permits nonsurgical treatment with immobilization and reduced activity and, ultimately, an improved outcome, whereas a delay in diagnosis can result in the need for surgical intervention. Physicians should encourage appropriate exercise for patients over 60 years of age but should also be aware of the possibility of stress fractures and the need for prompt diagnosis and treatment.
KARL E. MILLER, M.D.
Carpintero P, et al. Delayed diagnosis of fatigue fractures in the elderly. Am J Sports Med 1997 November;25:659-62.
Safety of Naltrexone for the Treatment of Alcoholism
The opioid antagonist naltrexone is the first new drug approved for use in the treatment of alcoholism in nearly 50 years. Croop and associates performed a nonrandomized open-label study to evaluate the safety profile of naltrexone.
The study was performed before approval of naltrexone and was sponsored by the manufacturer of the drug. The 12-week study was conducted at 40 alcoholism treatment centers throughout the United States. Patients in the study included 865 men and women over the age of 18 (age range: 18 to 73 years; mean age: 38.9 years) who had not ingested alcohol for one to six weeks. A total of 570 study subjects received naltrexone, and 295 served as the reference group. Both groups underwent the same evaluations during the study and participated in a psychosocial treatment program for alcoholism. The majority of the patients in the naltrexone group (69.9 percent) received 50 mg per day (dosage range: 25 mg every third day to 200 mg daily). Blood samples for hematologic evaluation and liver function studies were obtained at baseline and every four weeks for 12 weeks. All adverse clinical events were recorded at two-week intervals.
Approximately 80 percent of the patients in each group received concomitant medications during the study, including antidepressants, benzodiazepines and antipsychotic agents. After 12 weeks, 220 patients treated with naltrexone and 145 reference patients had completed the study.
Data on adverse events were available for 238 reference patients and 500 patients who received naltrexone. Of these patients, 37.6 percent of the naltrexone group and 17.6 percent of the reference group reported at least one adverse event during the study. Fifteen percent of the group that received naltrexone withdrew from the study because of adverse side effects, most commonly nausea, headache and dizziness. Serious adverse events were reported in 53 patients in the naltrexone group and in 12 patients in the reference group. However, most of the adverse events represented hospitalization because of relapse or depression, and none were believed to be related to naltrexone.
No significant laboratory abnormalities were noted. A significant decrease from baseline occurred in alanine aminotransferase levels (a very sensitive indicator of drug-induced hepatocellular injury) in both the naltrexone group and the reference group.
The authors conclude that naltrexone has a very broad safety profile for the treatment of alchoholism. No previously unreported adverse events were identified during this study.
JEFFREY T. KIRCHNER, D.O.
Croop RS, et al. The safety profile of naltrexone in the treatment of alcoholism: results from a multicenter usage study. Arch Gen Psychiatry 1997 December;54:1130-5.
Diagnostic Value of Cardiac Troponin in Acute Chest Pain
The relative lack of sensitivity and specificity of electrocardiography (ECG) and the serum creatine kinase-MB (CK-MB) level in acute coronary syndromes results in a large number of unnecessary admissions to coronary care units. Conversely, developing myocardial infarction is undetected in some patients, and these patients may be discharged from the emergency department. Hamm and colleagues studied the diagnostic value of the cardiac-specific contractile proteins troponin T and troponin I for the early triage of patients who visited an emergency department for evaluation of acute chest pain.
Patients included in the study presented to the emergency department because of acute anterior, precordial or left-sided chest pain of less than 12 hours' duration. The pain could not be explained by obvious trauma or by abnormalities on a chest radiograph. Patients were excluded if ST-segment elevation was apparent on ECG or if they had had an acute myocardial infarction within the previous two weeks. Blood was drawn within 15 minutes of arrival at the hospital for measurement of troponin T and troponin I. The tests were repeated four hours later and, if the patient presented with pain of less than two hours' duration, the troponin assays were repeated a third time at six hours after the onset of chest pain. The tests were performed by a trained assistant in the emergency department, and the results were immediately available to the treating physician.
A total of 773 patients were enrolled in the study, and 47 (6.1 percent) were diagnosed as having a myocardial infarction on the basis of routine measurements of CK-MB within 24 hours of presentation. Of these 47 patients, 24 (51 percent) had positive results on the troponin T test at the time of arrival in the emergency department and 44 (94 percent) had positive results four hours later. The troponin I results were positive in 31 (66 percent) of these patients on arrival, and all of the 47 patients had positive test results four hours later. Measurements of CK-MB were elevated in 25 (53 percent) of these patients on arrival in the emergency department and in 43 (91 percent) of these patients four hours later.
Unstable angina was the admitting diagnosis in 315 patients. Seventy patients (22.2 percent) had at least one positive troponin T measurement, and 114 (36.2 percent) had at least one positive troponin I value. CK-MB elevation at any time was found in only 16 (5.1 percent) of these patients.
Troponin assays were negative in 286 patients who were not admitted. Seven of these patients were subsequently found to have a positive result for troponin I on repeat testing at a separate laboratory. Two of these patients had adverse cardiac events soon after discharge, including a nonfatal myocardial infarction five days later and a presumed cardiac death 23 days later.
The authors conclude that troponin T and troponin I levels are highly sensitive for the diagnosis of myocardial infarction (94 percent for troponin T and 100 percent for troponin I). However, the diagnostic specificity for myocardial infarction was low: 22 percent of the patients with unstable angina had positive results for troponin T, and 36 percent had positive results for troponin I. For patients with two negative troponin values at least four hours apart, the likelihood of an acute coronary event was very low. Troponin T and troponin I tests result in more accurate diagnoses than previous, more time-comsuming methods
JEFFREY T. KIRCHNER, D.O.
Hamm CW, et al. Emergency room triage of patients with acute chest pain by means of rapid testing for cardiac troponin T or troponin I. N Engl J Med 1997 December; 337:1648-53.
Predicting Treatment Outcome in Chronic Hepatitis C
Infection with hepatitis C virus often leads to chronic hepatitis, after which cirrhosis and hepatocellular carcinoma may develop. Currently, interferon-alfa is the only treatment, and it must be administered for more than six months to be effective. Many factors influence treatment outcome, including patient age and duration of infection, absence of cirrhosis, body weight, gamma-glutamyl transpeptidase levels, viral genotype and pretreatment serum titer of hepatitis C RNA. However, these factors are not useful in predicting response to treatment in individual patients. Gavier and associates evaluated the predictive value of elimination of viremia after one month of treatment as a marker of successful treatment.
A total of 181 patients with chronic hepatitis C who had been treated with interferon-alfa for one year were included in the study. Laboratory values obtained before treatment showed alanine aminotransferase (ALT) concentrations 1.5 times above the normal range, positive results of antibody to hepatitis C virus testing and hepatitis C RNA serum testing, and histologic evidence of chronic hepatitis with or without cirrhosis. Treatment consisted of daily doses of interferon-alfa for two, three or four months, then three times a week for the remainder of the year. Median follow-up after treatment for all patients was 49 months. Patients were considered to have a sustained response if ALT levels remained within normal limits and serum HCV RNA levels were negative throughout the follow-up period. All other patients were considered nonresponders.
Fifty-one patients (28 percent) showed a sustained response to therapy. After one month of treatment, 68 of 132 tested patients had cleared hepatitis C virus RNA from serum. Among these 68 patients, one half showed a sustained response and one half were nonresponders. Of the 64 patients who remained viremic after one month of therapy, 61 were nonresponders, whereas only three had a sustained response. Transaminase levels obtained after the first and third months of therapy showed less significant association with the response. Several factors appear to be significantly associated with a higher probability of sustained response. Clearance of serum hepatitis C RNA after one month of treatment was the strongest independent predictor of sustained response. Negative viremia after one month of treatment resulted in a predicted probability of long-term response of 50 percent, with wide variability depending on age. Persistent viremia more accurately indicated a low probability of long-term response.
The authors conclude that early determination of viral status during therapy is the principal predictor of the final outcome of treatment. The negative predictive value of this measurement is quite high, although a small percentage of patients (less than 5 percent) would be misclassified as nonresponders. When viremia becomes negative, the probability of sustained response is likely to vary between 20 and 70 percent, depending on patient age. Withdrawal of treatment might be considered in patients who have not cleared hepatitis C virus RNA after one month, although in selected patients other potential benefits such as slower progression to cirrhosis and decreased risk of hepatocellular carcinoma should be considered.
RICHARD SADOVSKY, M.D.
Gavier B, et al. Viremia after one month of interferon therapy predicts treatment outcome in patients with chronic hepatitis C. Gastroenterology 1997 November;113:1647-53.
Use of the Ottawa Knee Rule for Evaluation of Knee Injuries
The Ottawa knee rule was developed to provide guidelines for the radiographic assessment of acute knee injuries (see the accompanying table). Implementation of the Ottawa knee rule has been shown to have the potential of decreasing the use of knee radiographs by 28 percent. Stiell and colleagues conducted a controlled clinical trial to assess the application of the Ottawa knee rule in clinical settings and its impact on the evaluation of acute knee injuries.
Ottawa Knee Rule for Obtaining Radiographs in Knee Injuries
The rightsholder did not grant rights to reproduce this item in electronic media. For the missing item, see the original print version of this publication. The study included over 3,000 adults who underwent treatment for acute knee injury at one of four hospitals. At two of the hospitals, physicians received a brief lecture about the Ottawa knee rule and a pocket guide for reference. In addition, posters of the Ottawa knee rule were displayed in the emergency department. Physicians were encouraged to use the Ottawa knee rule when deciding whether to order radiographs in patients with acute knee injuries. The other two hospitals served as control sites, and physicians at these hospitals did not receive instructions on the Ottawa knee rule.
After the Ottawa knee rule was emphasized in the two intervention hospitals, there was a relative reduction of 26.4 percent in the proportion of patients referred for knee radiographs, compared with a 1.3 percent relative reduction at the two control sites. The Ottawa knee rule was interpreted accurately by the physicians 97.7 percent of the time at the intervention hospitals.
In 3.5 percent of cases, radiographs were ordered even though adherence to the knee rule would not have led to a decision to obtain radiographs. None of these patients had fractures. Reasons for not following the Ottawa knee rule in these patients included the physician's disagreement with the rule, the patient's or orthopedic consultant's insistence on radiographs and unreliable physical examination because the patient was intoxicated.
The Ottawa knee rule was found to have a sensitivity of 1.0 and a negative predictive value of 1.0 by correctly identifying all 58 of the clinically important fractures in the study population. Nearly all of the patients (98.7 percent of those undergoing radiography and 95.7 percent of those who did not have radiographic examinations) were satisfied with the care they received for their knee injuries. Patients who were discharged without undergoing radiography had shorter stays in the emergency department (85.7 minutes versus 118.8 minutes) and incurred lower costs ($80 versus $183).
The authors conclude that the Ottawa knee rule can reduce the use of knee radiographs without compromising patient satisfaction and patient care.
GRACE BROOKE HUFFMAN, M.D.
Stiell IG, et al. Implementation of the Ottawa knee rule for the use of radiography in acute knee injuries. JAMA 1997 December 17;278:2075-9.
Interferon-Alfa Treatment of Chronic Hepatitis B
Chronic infection with hepatitis B is one of the leading causes of chronic hepatitis and cirrhosis and is possibly the major cause of hepatocellular carcinoma worldwide. While there is no definitive cure, interferon-alfa has been reported to induce remission in 25 to 40 percent of patients. However, follow-up has been limited to one to two years in these patients, which is inadequate to determine their ultimate prognosis. Lau and associates evaluated long-term survival rates and clinical outcomes in patients with chronic hepatitis B who were treated with interferon-alfa.
A total of 103 patients with chronic hepatitis B were evaluated after receiving treatment with interferon-alfa in three clinical trials. Before treatment, all of the study subjects had elevated serum levels of aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) for at least six months, and hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and hepatitis B virus DNA were present in serum. Results of pretreatment liver biopsies revealed that all patients had histologic evidence of chronic hepatitis B. A beneficial response to treatment was defined as a sustained loss of hepatitis B virus DNA from serum and subsequent clearance of HBeAg within one year of treatment.
Thirty-one patients (30 percent) were considered responders and 72 (70 percent) nonresponders. Responders were more frequently female and black and had a significantly lower level of hepatitis B virus DNA and higher levels of AST and ALT. Of the 31 responders, 10 (32 percent) had cirrhosis, compared with only seven (10 percent) of nonresponders. Reactivation of hepatitis B, defined as reappearance of HBeAg or hepatitis B virus DNA in serum, occurred in two of 31 responders and five of 37 nonresponders. By survival analysis, the rate of mortality from all causes was similar for the two groups nine years after treatment. Liver-related deaths or complications were more frequent among nonresponders than responders, but the difference was not statistically significant. The presence of cirrhosis significantly increased the risk of poor outcome.
The authors conclude that patients with chronic hepatitis B who demonstrate a serologic response to interferon-alfa therapy experience fewer liver-related complications. Improvements are particularly striking among patients who had pretreatment cirrhosis resulting from hepatitis B. Some patients who lost HBsAg still had mildly active liver disease and hepatitis B virus DNA in serum. Portal hypertension and complications of liver disease eventually developed among those with preexisting cirrhosis.
RICHARD SADOVSKY, M.D.
Lau D, et al. Long-term follow-up of patients with chronic hepatitis B treated with interferon alfa. Gastroenterology 1997 November;113;1660-7.
Seven-Day Triple Combination Therapy for Helicobacter pylori
Optimal treatment for Helicobacter pylori infection in patients with dyspeptic syndromes is unclear at the present time since the incidence of H. pylori resistance to metronidazole has increased. Chey and colleagues studied the effect of triple therapy with a proton pump inhibitor, clarithromycin and metronidazole or bismuth subsalicylate for seven days in the treatment of documented H. pylori infection in patients with peptic ulcer disease, a history of peptic ulcer disease or nonulcer dyspepsia.
None of the 112 patients who were enrolled in the study had received previous treatment for H. pylori infection. Patients were randomly assigned to one of two treatment groups. The first group received lansoprazole in a dosage of 30 mg twice a day, clarithromycin in a dosage of 500 mg twice a day, and metronidazole in a dosage of 500 mg twice a day. The second group received the same dosages of lansoprazole and clarithromycin but were given bismuth subsalicylate in a dosage of 524 mg twice a day as the third agent instead of metronidazole. Both treatments lasted seven days.
Both regimens eradicated H. pylori in over 80 percent of patients, with no significant difference between the two groups. The most common side effects reported in the metronidazole-treated group were altered taste (39 percent) and abdominal pain (19 percent); side effects reported in the bismuth subsalicylate-treated group were altered taste (23 percent) and dark stools (23 percent). No patients dropped out of the study because of intolerable side effects.
The authors conclude that both triple regimens are successful in eradicating H. pylori. Both regimens were well-tolerated, and there were no side effects resulting in discontinuation of therapy. The authors suggest that because there is an increasing potential for H. pylori to become resistant to metronidazole, bismuth subsalicylate may be a viable alternative.
KARL E. MILLER, M.D.
Chey WD, et. al. Bismuth subsalicylate instead of metronidazole with lansoprazole and clarithromycin for Helicobacter pylori infection: a randomized trial. Am J Gastroenterol 1997 September;92:1483-6.
Transvaginal Ultrasonography vs. Endometrial Biopsy
A limitation of endometrial biopsy is the difficulty in obtaining an adequate sample in some patients. Transvaginal ultrasonography has been recommended by some clinicians as an alternative to endometrial biopsy. Langer and colleagues, as part of the Postmenopausal Estrogen/Progestin Interventions (PEPI) trial, compared transvaginal ultrasonography with endometrial biopsy for the detection of endometrial hyperplasia in asymptomatic postmenopausal women.
The 875 women in the PEPI study were between 45 and 64 years of age and were postmenopausal for no longer than 10 years. All of the women received 0.625 mg of conjugated estrogen daily. Treatment groups included estrogen alone and several different dosing regimens of progesterone. Endometrial biopsies were normal at baseline in all of the participants and were repeated annually thereafter during the three years of the study. All biopsy specimens were evaluated by at least two pathologists. Approximately halfway through the study, transvaginal ultrasonography was added to the annual evaluation. This procedure was always performed within 48 hours before the endometrial biopsy.
A total of 448 women were included in the ultrasound portion of the PEPI study, and 577 transvaginal ultrasound examinations were performed. On the basis of data from four previous studies, 4 mm was selected as the maximal normal endometrial thickness. Endometrial thickness was greater than 4 mm in 307 (53.2 percent) of the 577 ultrasound examinations. Biopsy results were abnormal in 31 instances, or 5.4 percent of the 577 examinations. Most abnormal biopsy results were simple endometrial hyperplasia.
When the results of transvaginal ultrasonography were compared with histopathologic findings, a 5-mm threshold for abnormal endometrial thickness had a 90 percent sensitivity and a 48 percent specificity for detecting endometrial disease. The positive predictive value was 9 percent, and the negative predictive value was 99 percent; 53 percent of the women with normal biopsy results had an endometrial thickness of at least 5 mm. When simple hyperplasia was excluded from the analysis of patients with abnormal biopsy results, the positive predictive value of an endometrial thickness of more than 5 mm was low (i.e., 12 percent) in these high-risk patients.
The authors conclude that transvaginal ultrasonography is useful in detecting endometrial hyperplasia in asymptomatic women receiving hormone replacement therapy, but the high false-positive rate associated with ultrasonography makes it a poor screening test for following asymptomatic women whether or not they are receiving hormone replacement therapy.
JEFFREY T. KIRCHNER, D.O.
Langer RD, et al. Transvaginal ultrasonography compared with endometrial biopsy for the detection of endometrial disease. N Engl J Med 1997 December 18;337:1792-8. Fleischer AC. Optimizing the accuracy of transvaginal ultrasonography of the endometrium [Editorial]. N Engl J Med 1997 December 18;337;1839-40.
EDITOR'S NOTE: My interpretation of this study is that transvaginal ultrasonography is not a very good diagnostic alternative to endometrial biopsy in women receiving hormone replacement therapy. Other studies have found that the endometrial thickness does not normally exceed 4 to 5 mm in postmenopausal women. However, a significant number of women in this study had normal results on endometrial biopsy and an endometrial thickness of 5 to 9 mm. In an accompanying editorial, Fleischer cites a study in which estimates of endometrial thickness in the same patient differed by up to 1.5 mm among radiologists. Interestingly, he supports the use of transvaginal ultrasonography, both for monitoring the endometrial response to hormone replacement therapy and for evaluating unexplained vaginal bleeding. Since transvaginal ultrasonography can detect disease in the absence of symptoms, he believes it deserves a place in the routine evaluation of perimenopausal and, particularly, postmenopausal women. I believe the data suggest that family physicians should continue to perform endometrial biopsy as the diagnostic procedure of choice in symptomatic patients. The data do not suggest that transvaginal ultrasonography is of benefit in screening asymptomatic women.
J.T.K.
Polymerase Chain Reaction and Hepatitis C Transmission
Although much has been learned about routes of infection of hepatitis C, it is still difficult to advise patients about their risk of infection following specific exposures. The development of polymerase chain reaction methods for detecting hepatitis C RNA has provided the potential for assessing the infectiousness of people who are positive for the hepatitis C virus. Dore and colleagues reviewed the literature concerning transmission of the hepatitis C virus to assess the role of polymerase chain reaction in estimating the infectiousness of people with the hepatitis C virus.
The authors searched Medline and Embase databases plus bibliographies of published papers to identify all published studies examining the transmission of hepatitis C from patients testing positive for the virus. Only studies using the polymerase chain reaction with or without other tests to establish infection status were included in this review.
Of the 29 studies published between 1992 and 1996, 21 studies examined vertical hepatitis C transmission from pregnant mothers; three studied hepatitis C transmission after bone marrow or solid organ donation; three studied transmission after blood transfusion; and two studies examined transfusion after needlestick exposures among health care workers. Data were available on a total of 2,022 people exposed to sources positive for hepatitis C infection. Among the 1,148 persons exposed to sources testing positive by polymerase chain reaction, 148 cases of confirmed transmission occurred.
The rate of transmission of hepatitis C among the 903 children born to mothers with hepatitis C infection and positive polymerase chain reaction ranged up to 42 percent, with a combined rate from all studies of 6.2 percent. Five studies confirmed higher rates of vertical transmission when the mother had a high level of viremia. Positive human immunodeficiency virus (HIV) infection status was also associated with higher rates of vertical transmission in mothers with hepatitis C antibody and was estimated to be 15.8 percent (range: 11.8 to 19.8 percent). In one study, vertical transmission was significantly increased in infants delivered vaginally compared with infants delivered by cesarean section (32 percent versus 6 percent), but no association could be demonstrated between hepatitis C transmission and breast-feeding. Measures of maternal hepatic function and infection with specific hepatitis C genotypes did not appear to influence the risk of vertical transmission of infection.
Studies of transplantation recipients showed very high rates of transmission of hepatitis C infection (78 percent; range: 72 to 94 percent) when the polymerase chain reaction was positive in the donor. Similarly, studies of recipients of blood transfusions showed transmission rates of 74 to 92 percent, with a pooled estimate of 83 percent. Only two studies examined risk to health care workers following needlestick injuries from patients with confirmed hepatitis C infection. The pooled estimate from these studies was 6.1 percent (range: 2.3 to 9.9 percent).
The authors estimate the current risk for infection when the polymerase chain reaction is positive in the infection source to be 6.2 percent after perinatal exposure, 6.1 percent following needlestick exposure, 78 percent after transplant exposure and 83 percent following transfusion of blood infected with hepatitis C.
The authors conclude that based on the evidence from studies of vertical transmission, the level of viremia and coinfection with HIV are important risk factors for transmission that deserve further study. The authors also believe that the viral genotype could be a factor in the degree of risk of transmission. The probability of infection from a source who has antibodies to hepatitis C but negative polymerase chain reaction is extremely small and may in fact pose "virtually no risk." This point may be extremely important when counseling patients at risk for transmitting hepatitis C and those exposed to infective sources, particularly health care workers who have antibodies to hepatitis C.
ANNE D. WALLING, M.D.
Dore GJ, et al. Systematic review of role of polymerase chain reaction in defining infectiousness among people infected with hepatitis C virus. BMJ 1997 October; 315:333-7.
Benefits of Tight Glycemic Control in Type 2 Diabetes
Progression of microvascular disease in patients with diabetes can result in blindness and renal failure. Intensive glycemic control is important in patients with insulin-dependent (type 1) diabetes mellitus to reduce the risk of complications associated with microvascular disease. These problems affect patients with noninsulin-dependent (type 2) diabetes less frequently, so the benefits of tight control in this patient group are less convincing. Vijan and associates created a model to calculate the risks associated with development of blindness and end-stage renal disease in patients at different ages of diabetes onset and for levels of glycemic control.
Patients were assumed to have no clinically detectable complications of microvascular disease at the time of diagnosis. Patients with complications at the time of diagnosis are at high risk, and intensive glycemic control should be considered. The risks for end-stage outcomes are highest in patients who are diagnosed with diabetes at a young age and in those who have poor glycemic control.
In patients with type 2 diabetes, the risks of complications and the benefits of increased glycemic control are less clear. Improving glycemic control reduces the risk of microvascular complications in patients who are diagnosed with type 2 diabetes at a young age, and tight glycemic control is indicated for these patients. However, definitive evidence that moderate glycemic control provides much benefit to patients diagnosed with type 2 diabetes later is lacking.
The authors conclude that their model adequately estimates which patients are most likely to benefit from intensified glycemic control. Those with late-onset diabetes benefit less from intensified glycemic control, although in some cases, because of high short-term risk and potential benefit, interventions in older patients have as much or more value as interventions in younger patients. Targeting specific patients who are at high risk is likely to achieve the most benefit.
In an editorial in the same issue, Skyler notes that the evidence supporting tight glycemic control for patients with type 1 diabetes should be generalized to those with type 2 diabetes, citing that the American Diabetes Association Standards of Care recommend striving for tight glycemic control in all patients with diabetes. He points out that the use of simulation models, such as that used by Vijan and associates, are theoretic and require validation. However, he concedes that elderly patients with type 2 disease may not need treatment as aggressive as that required in younger patients. He calls for more research so that treatment programs may be developed that focus on improved glycemic control for all patients with diabetes.
RICHARD SADOVSKY, M.D.
Vijan S, et al. Estimated benefits of glycemic control in microvascular complications in type 2 diabetes. Ann Intern Med 1997 November;127:788-95, and Skyler JS. Glucose control in type 2 diabetes mellitus [Editorial]. Ann Intern Med 1997 November;127:837-8.
EDITOR'S NOTE: The debate about the value of tight glycemic control in patients with type 2 diabetes continues. Some evidence indicates that maintaining euglycemia through diet, exercise and medication delays vascular complications, depending on individual characteristics such as age and the presence or absence of microvascular disease at the time of diagnosis. Problems such as hypoglycemia and poor patient compliance make individualization of glycemia goals critical in these patients, even with the current recommendations of the American Diabetes Association. One specific recommendation for all patients may not be appropriate at this time.--r.s.
PotassiumMagnesium Citrate to Prevent Nephrolithiasis
Potassium citrate has been shown to be effective prophylaxis against recurrent calcium oxalate nephrolithiasis, but its use is limited because of gastrointestinal side effects. Studies suggest that recurrent calcium oxalate stones may be related to magnesium deficiency. In response to these two issues, a formulation of potassiummagnesium citrate was developed by clinical investigators. This formulation has a lower concentration of potassium and may reduce the incidence of gastrointestinal side effects. Ettinger and colleagues studied the effectiveness of potassiummagnesium citrate in the prevention of nephrolithiasis in patients with recurrent stone formation.
Patients were included in the placebo-controlled study if they had a history of two or more calcium oxalate calculi in the previous five years and at least one episode within the previous two years with no secondary causes. One group of 31 patients received potassiummagnesium citrate therapy, which provided a daily dosage of 42 mEq of potassium, 21 mEq of magnesium and 63 mEq of citrate. The placebo group included 33 patients. Initial assessment included 24-hour urine studies, blood chemistries, evaluation for the possibility of current stones and assessment of previous nephrolithiasis. The 24-hour urine studies and blood chemistries were repeated five months later and then every four months during the three years of the study. Side effects of treatment were evaluated at each visit.
At the end of three years, only 13 percent of the treatment group had recurrent nephrolithiasis, compared with 64 percent of the placebo group. Approximately one half of the patients in the treatment group dropped out of the study, but only 16 percent did so because of adverse side effects.
The authors conclude that the potassiummagnesium citrate formulation is effective as prophylaxis against recurrent calcium oxalate stones. This formulation did not cause hypocitraturia, so this parameter would not need monitoring. Gastrointestinal side effects were less frequent with potassiummagnesium citrate than with potassium citrate, but the authors note that the incidence of side effects should be studied further.
KARL E. MILLER, M.D.
Ettinger B, et al. Potassium-magnesium citrate is an effective prophylaxis against recurrent calcium oxalate nephrolithiasis. J Urol 1997 December;158:2069-73.
Serum Lactate as a Marker of Acute Myocardial Infarction
Five million patients visit emergency departments annually with a chief complaint of chest pain, although fewer than 15 percent are diagnosed with acute myocardial infarction. Early diagnosis of acute myocardial infarction in patients with acute onset of chest pain continues to be a problem. Information obtained on presentation, such as the patient's clinical history, baseline vital signs and initial electrocardiogram (ECG) readings, is often unreliable, and rapid assays of creatine phosphokinase (CK), CK-MB subforms, and troponin T and troponin I may not rise for six to 12 hours. Serum lactate, however, is a well established marker of inadequate systemic perfusion and resulting tissue hypoxia. Schmiechen and associates evaluated the question of whether serum lactate levels could be used to confirm a diagnosis of acute myocardial infarction or other acute illness in patients with acute chest pain.
All patients aged 18 years and older who visited the emergency department within 24 hours of experiencing chest pain or other cardiac symptoms were eligible for inclusion in the study. On presentation, blood samples were obtained to evaluate serum lactate levels. A positive lactate finding was defined as a blood lactate concentration of 13.5 mg per dL (1.5 mmol per L) or greater. In addition, serial CK and CK-MB levels and ECG readings were obtained, along with standard vital signs and a medical history, which were used by physicians in the cardiology department to make the diagnosis of acute myocardial infarction.
Of the 129 patients who were included in the study, 28 had a documented acute myocardial infarction. The mean patient age was 58 years, and the ratio of men to women was 1.6:1. All but one of the patients with acute myocardial infarction had a positive serum lactate finding. Of the 101 patients in the group without acute myocardial infarction, 46 had positive serum lactate levels. The overall sensitivity of a positive lactate finding for acute myocardial infarction was 96 percent, and the specificity was 55 percent. This yields a negative predictive value of 98 percent and a positive predictive value of 37 percent. Fourteen of the patients with acute myocardial infarction had normal CK and CK-MB values at the time of admission; however, the CK-MB levels eventually increased in all of these patients. Vital signs did not significantly differ in either group.
The authors conclude that, unlike adjuncts typically used to diagnose acute myocardial infarction, serum lactate levels measured within three hours of the onset of symptoms are highly sensitive for acute myocardial infarction, significantly more so than CK and CK-MB levels measured at that time. The level of serum lactate is thought to rise rapidly in patients with acute myocardial infarction because of poor systemic perfusion secondary to uncompensated cardiac ischemia. However, the low specificity of lactate means that it should not be used in place of CK and CK-MB determinations to direct thrombolytic therapy. Hyperlactemia also appears to correlate with critical illness and mortality in patients presenting with chest pain. The authors note that the use of lactate levels may be limited, since conditions such as renal insufficiency, smoke inhalation, seizures and alcohol intoxication tend to cause unreliably elevated lactate levels. However, patients with normal lactate levels, medical history and ECG findings could be considered at low risk for acute myocardial infarction and may benefit from this quick, simple, inexpensive "rule out" test.
RICHARD SADOVSKY, M.D.
Schmiechen NJ, et al. ED use of rapid lactate to evaluate patients with acute chest pain. Ann Emerg Med 1997 November;30:571-7.
Maintenance of Cardiac Health in Older Adults
Although survival rates in patients with heart disease are improving, coronary heart disease remains the leading cause of morbidity and mortality in adults over 65 years of age. More older adults are living longer with chronic heart disease. The prevalence of heart disease increases with age and is one of the major causes of disability associated with aging. Heart disease also interacts with other diseases such as arthritis to synergistically increase the degree of disability. Shortness of breath is the most common symptom associated with decreased exercise tolerance. Fried and associates review the risk factors for cardiovascular disease in older adults and discuss prevention strategies.
Risk factors for myocardial infarction in older adults include elevated systolic blood pressure, cigarette smoking and elevated serum glucose levels. Subclinical cardiovascular disease is associated with a number of risk factors also associated with clinical disease. These include age, elevated systolic blood pressure, fasting glucose levels, high blood pressure and smoking in both men and women and, in addition, in women, diastolic blood pressure, low-density lipoprotein-cholesterol levels, high-density lipoprotein-cholesterol levels and leukocyte count. These data point to the importance of behavioral risk factors.
Cardiovascular changes that occur with aging include structural changes in the arterial vessel wall that lead to decreased vascular elasticity and result in an increase in systolic blood pressure and afterload. Resulting myocardial changes include left ventricular wall thickening and decreased left ventricular compliance. Diastolic abnormalities can be seen on echocardiography. Systolic function is less affected by the aging process. The resting ejection fraction does not appear to change with age. The resting heart rate and cardiac output remain relatively constant because of an increase in catecholamine levels offsetting decreased beta-adrenergic receptor activity. Overall, the resting heart adapts well to the structural and functional changes associated with aging.
Exercise emphasizes age-associated cardiovascular system changes. Notably, maximum oxygen consumption with exercise decreases substantially. Older adults increase their end-diastolic volume through the Frank-Starling mechanism to increase cardiac output during exercise. In the presence of stressors on the heart, such as exercise, the ability to increase heart rate and contractility is impaired in older adults, as is oxygen extraction by functioning myocardium. An exercise training program, defined as 30 minutes of strenuous exercise three to four times a week for several years, can attenuate some of the adverse age-related changes that occur in the cardiovascular system. Exercise training can also positively affect body fat, blood pressure, cholesterol level and muscle mass.
The authors conclude that modifying risk factors by stopping smoking, controlling blood pressure and managing glucose levels is the key to improved cardiac health. Exercise training appears to be clearly beneficial in augmenting primary and secondary prevention, including directly reducing the incidence of myocardial infarction and lessening the symptoms of angina.
RICHARD SADOVSKY, M.D.
Fried LP, et al. Heart health in older adults. Import of heart disease and opportunities for maintaining cardiac health. West J Med 1997 October;167:240-6.
EDITOR'S NOTE: Primary and secondary prevention of cardiac disease in the older adult has well-documented beneficial effects, including a decrease in cardiovascular disease and disability rates. In addition, an increased sense of well-being and functional capacity have been documented. Family physicians can encourage patients to initiate regular exercise programs in a manner most applicable to the individual patient's interests and values. Some patients will do well with organized exercise groups while others will prefer more individualized programs. Exercise should be initiated slowly and steadily increased to the recommended 30 minutes of strenuous aerobic exercise at least three times per week. Patients who need motivation may do best under direct supervision, increasing their heart rates at maximal exercise to 60 to 80 percent of maximum for their age
R.S.
Functional Decline as It Relates to Specific Medical Conditions
Little is known about the varying degrees of functional decline associated with certain conditions alone or in combination with other conditions. Kiely and colleagues conducted a longitudinal study to assess how functional decline varies among patients with heart disease, arthritis, diabetes, cancer and stroke, either alone or in combination.
Elderly persons living in the community and residents of a home care program participated in this study. The study subjects ranged in age from 69 to 101 years (median age: 86 years). A baseline assessment and two annual follow-up assessments were conducted. Almost all of the study subjects were interviewed by telephone. A functional dependency index was calculated from each person's scores on activities of daily living and on instrumental activities of daily living. An increase in the functional dependency index was considered a functional decline.
Of the 1,060 patients initially interviewed, 931 (87.8 percent) completed the first follow-up assessment and 822 (77.5 percent) completed the second assessment. During the first interview, 65 percent of the patients reported having arthritis; 37 percent, heart disease; 15 percent, diabetes mellitus; 11 percent, stroke; and 8 percent, cancer.
Functional decline occurred throughout the study period: 53.2 percent were independent at baseline, 47.1 percent were independent at the one-year assessment, and 40.6 percent remained independent at the two-year assessment. The rate of decline did not differ significantly among the patients with different medical conditions. However, a significant decline in functional status occurred with each additional diagnosis in an individual patient. Stroke, the condition most strongly associated with functional impairment, was comparable to a five-year maturational decline. Coexistent heart disease and diabetes mellitus compared with a two-year maturational decline, and the presence of arthritis and cancer was comparable to a one-year maturational decline.
The authors conclude that prevention of certain medical conditions, particularly stroke, is necessary to maintain a patient's functional level. They propose further research to determine whether aggressive rehabilitation programs initiated immediately after the diagnosis of one of the conditions studied can prevent the functional decline associated with the condition.
GRACE BROOKE HUFFMAN, M.D.
Kiely DK, et al. The effect of specific medical conditions on functional decline. J Am Geriatr Soc 1997 December;45:1459-63.
Thromboembolic Disease and Factor V Leiden Defect
Patients diagnosed with thromboembolic disease at a young age, or those who have a family history or recurrent episodes of the disease, typically undergo a battery of laboratory studies to identify inherited disorders of hemostasis. This work-up generally consists of measuring serum levels of antithrombin III, protein C and protein S, as well as performing qualitative and quantitative assays for fibrinogen. An unusual mutation in the hemostatic pathway, discovered in 1993, has had a profound effect on the way in which thromboembolic disease can be diagnosed and ultimately treated. This defect is referred to as resistance to activated protein C. A single gene mutation in the coding for coagulation factor V, known as factor V Leiden, makes the activated form of factor V (Va) relatively resistant to degradation by activated protein C. Price and Ridker reviewed the literature on factor V Leiden to identify the prevalence and risks of thromboembolism associated with this mutation and suggest methods for diagnosis and treatment.
Factor V Leiden mutation is rather common, affecting 3 to 7 percent of the population in Europe and the United States. It most commonly affects whites and is significantly less prevalent in other ethnic groups, most notably Asian and black populations. Patients who are homozygous for the mutation present with the disease at a younger age than those who are heterozygous for the mutation. In addition, the risks associated with this mutation appear to increase with age. The presence of factor V Leiden is associated with increased risk for primary and recurrent venous thromboembolism and for venous thromboembolism with use of oral contraceptives and during pregnancy. However, it does not appear to affect the incidence of arterial thromboembolism.
Definitive diagnosis of the mutation requires the use of techniques based on polymerase chain reaction, although resistance to activated protein C may also be identified using relatively simple plasma testing. These tests are less reliable if the patient is taking anticoagulant therapy or has lupus anticoagulant. The presence of protein S deficiency does not appreciably alter the results of plasma testing. Newer assay methods that use factor V-deficient plasma appear to be more reliable and are now available commercially. Positive results of plasma testing are usually followed by genetic confirmation of the mutation.
The authors conclude that the issues associated with screening for factor V Leiden are complex. Screening protocols for primary prevention are likely to be inefficient because the lifetime risk for venous thromboembolism in the general population is low. In fact, prescribing long-term anticoagulant therapy to affected persons may be hazardous. Among groups at higher risk, such as pregnant women and young women using oral contraceptives, the effectiveness of screening is also uncertain because of the hazards of anticoagulant therapy and the extremely low risk rates that would require massive screening programs to prevent possibly only one death per year. Screening does appear to be appropriate in persons with a family or personal history of venous thrombotic episodes, especially if the person is found to be homozygous.
RICHARD SADOVSKY, M.D.
Price DT, Ridker PM. Factor V Leiden mutation and the risks for thromboembolic disease: a clinical perspective. Ann Intern Med 1997 November;127:895-903.
EDITOR'S NOTE: The frequency of factor V Leiden mutation as a cause of venous thromboembolic disease needs to be recognized. Patients with venous thromboses must be screened for the presence of this mutation. The efficacy of management with anticoagulant therapy requires further study.--r.s. *
"Tips from Other Journals" are written by the medical editors of American Family Physician.
Copyright © 1999 by the American Academy of Family Physicians.
This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP.
